NMR spectroscopy has been used to concurrently measure very low density lipoprotein (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) as VLDL, LDL and HDL particle subclasses from in vitro blood plasma or serum samples. See, FIG. 1 and U.S. Pat. Nos. 4,933,844 and 6,617,167, the contents of which are hereby incorporated by reference as if recited in full herein. Generally stated, to evaluate the lipoproteins in a blood plasma and/or serum sample, the amplitudes of a plurality of NMR spectroscopy derived signals within a chemical shift region of the NMR spectrum are derived by deconvolution of the composite methyl signal envelope or spectrum to yield subclass concentrations.
The subclasses are represented by many (typically over 60) discrete contributing subclass signals associated with NMR frequency and lipoprotein diameter as shown in FIG. 2. As shown in FIG. 3A, the NMR evaluations can interrogate the NMR signals to produce concentrations of different subpopulations shown as seventy-three discrete subpopulations, 27 for VLDL, 20 for LDL and 26 for HDL. These sub-populations can be further characterized as associated with a particular size range within the VLDL, LDL or HDL subclasses.
Conventionally, a patient's overall risk of coronary heart disease (CHD) and/or coronary artery disease (CAD) has been assessed based on measurements of cholesterol content of a patient's LDL and HDL particles (LDL-C, HDL-C) rather than the numbers of these particles. These two risk factors are used to assess a patient's risk, and treatment decisions may be made to reduce the “bad” cholesterol (LDL-C) or increase the “good” cholesterol (HDL-C).
In the past, “advanced” lipoprotein test panels have typically included a total high density lipoprotein particle (HDL-P) measurement (e.g., HDL-P number) and a total low density lipoprotein particle (LDL-P) measurement (e.g., LDL-P number). The particle numbers represent the concentration in units such as nmol/L (for LDL-P) or μmol/L (for HDL-P). A total HDL-P number, the sum of the concentration values of each of the three sub-groups of HDL-P subclasses, can provide CHD risk assessment information that may be more accurate or complement HDL-C. It has also been proposed that large and small HDL particle subclasses do not confer the same anti-atherogenic potential. See, e.g., U.S. 2007/0264677, the contents of which are hereby incorporated by reference as if recited in full herein.
It is believed that LDL-P is a better indicator of risk of CHD relative to LDL-C as well as for therapy decisions. However, there are still open questions about the different functions of HDL and how to best evaluate CHD risk associated with a patient's HDL. See, e.g., Kher at el., Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Athersclerosis, N Engl. J. Med. 364: 127-135 (Jan. 13, 2011); Navab et al., HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms, Nat. Rev. Cardiol., 8, 222-232 (2011); and Alan Fogelman, When good cholesterol goes bad, Nat. Med., Vol. 10, No. 9, pp. 902-903 (September 2004), the contents of which are hereby incorporated by reference as if recited in full herein.
The mechanisms by which HDL can be protective or non-protective as associated with a person's risk of developing atherosclerosis or heart disease are complex and multifactorial. See, Farmer et al., Evolving Concepts of the Role of High-Density Lipoprotein in Protection from Athersclerosis, Curr Atheroscler Rep (2011) 13:107-114, the contents of which are hereby incorporated by reference as if recited in full herein.